CA1327942C - Antibacterial antiplaque, anticalculus oral composition - Google Patents
Antibacterial antiplaque, anticalculus oral compositionInfo
- Publication number
- CA1327942C CA1327942C CA000557661A CA557661A CA1327942C CA 1327942 C CA1327942 C CA 1327942C CA 000557661 A CA000557661 A CA 000557661A CA 557661 A CA557661 A CA 557661A CA 1327942 C CA1327942 C CA 1327942C
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- oral composition
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- agent
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- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8164—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical, and containing at least one other carboxyl radical in the molecule, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers, e.g. poly (methyl vinyl ether-co-maleic anhydride)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/0005—Components or details
- B05B11/0037—Containers
- B05B11/0039—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means
- B05B11/0044—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means compensating underpressure by ingress of atmospheric air into the container, i.e. with venting means
- B05B11/00446—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means compensating underpressure by ingress of atmospheric air into the container, i.e. with venting means the means being located at the bottom of the container or of an enclosure surrounding the container
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
- B05B11/1042—Components or details
- B05B11/1052—Actuation means
- B05B11/1053—Actuation means combined with means, other than pressure, for automatically opening a valve during actuation; combined with means for automatically removing closures or covers from the discharge nozzle during actuation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/87—Application Devices; Containers; Packaging
Abstract
ANTIBACTERIAL ANTIPLAQUE, ANTICALCULUS ORAL COMPOSITION
ABSTRACT
An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4' -trichloro-21-hydroxydiphenyl ether (Triclosan)*.
*Trade-mark
ABSTRACT
An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4' -trichloro-21-hydroxydiphenyl ether (Triclosan)*.
*Trade-mark
Description
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,I This lnventlon relates to an antibacterial antlplaque ¦
ianticalculus oral composltlon. More particularly, lt relates to an oral compositlon containing 8 polyphosphate anticalculus (that i6, antltartar) agent and a compatible antlbacterial agent effective to ¦inhibit plaque.
¦ In U.S. Patents 4,627,977 to Gaffar et al; ~,515~772 to Parran !j et al; and 4,323,551 to Parran, oral composltions are descrlbed which lnclude various polyphosphate compounds. In the patent to Gaffar et al, a linear molecular dehydrated polyphosphate salt 18 employed ln ;conjunctlon with a fluorlde lon-provldlng source and a synthetlc llnear ipolymerlc polycarboxylate to inhibit calculus formatlon.
.1 In the patents to Parran et al and to Parran water soluble ~dialkali metal pyrophosphate alone or mlxed with tetraalkali metal pyrophosphate is employed.
, Oral compositions whlch inhlblt calculus formatlon on deneal '6urfaces are hlghly desirable slnce calculus 18 one of the causitive '¦factors ln perlodontal condltlons. Thus, lts reductlon promotes oral ! ! hyg~ene.
i, ¦ Dental plaque is a precursor of calculus. Unllke calculus, ,Ihowever, plaque may form on any part of the tooth surface, particularly includlng at the glngival margin. Hence, besldes belng unslghtly, lt ~ll8 lmpllcated ln the occurence of glnglvltls. ! ::
¦ li Accordlngly, it would be hlghly deslrable to lnclude ¦ ¦lantlmlcroblal agents whlch have been known to reduce plaque in oral ;composltlons containlng antlcalculus agents. Indeed, thls has been de8cribed ln U.S. Patent 4,022,880 to Vlnson et al, whereln a compound ~!provldlng zlnc lons as an antlcalculus agent 18 admlxed wlth an an~ibacterlal agent effectlve to retard the growth of plaque bacteria.
A wlde varlety of antlbacterlal agents are described wlth the zinc . .
,I This lnventlon relates to an antibacterial antlplaque ¦
ianticalculus oral composltlon. More particularly, lt relates to an oral compositlon containing 8 polyphosphate anticalculus (that i6, antltartar) agent and a compatible antlbacterial agent effective to ¦inhibit plaque.
¦ In U.S. Patents 4,627,977 to Gaffar et al; ~,515~772 to Parran !j et al; and 4,323,551 to Parran, oral composltions are descrlbed which lnclude various polyphosphate compounds. In the patent to Gaffar et al, a linear molecular dehydrated polyphosphate salt 18 employed ln ;conjunctlon with a fluorlde lon-provldlng source and a synthetlc llnear ipolymerlc polycarboxylate to inhibit calculus formatlon.
.1 In the patents to Parran et al and to Parran water soluble ~dialkali metal pyrophosphate alone or mlxed with tetraalkali metal pyrophosphate is employed.
, Oral compositions whlch inhlblt calculus formatlon on deneal '6urfaces are hlghly desirable slnce calculus 18 one of the causitive '¦factors ln perlodontal condltlons. Thus, lts reductlon promotes oral ! ! hyg~ene.
i, ¦ Dental plaque is a precursor of calculus. Unllke calculus, ,Ihowever, plaque may form on any part of the tooth surface, particularly includlng at the glngival margin. Hence, besldes belng unslghtly, lt ~ll8 lmpllcated ln the occurence of glnglvltls. ! ::
¦ li Accordlngly, it would be hlghly deslrable to lnclude ¦ ¦lantlmlcroblal agents whlch have been known to reduce plaque in oral ;composltlons containlng antlcalculus agents. Indeed, thls has been de8cribed ln U.S. Patent 4,022,880 to Vlnson et al, whereln a compound ~!provldlng zlnc lons as an antlcalculus agent 18 admlxed wlth an an~ibacterlal agent effectlve to retard the growth of plaque bacteria.
A wlde varlety of antlbacterlal agents are described wlth the zinc . .
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1 3 2 7 9 ~ 2 compounds includ .g cationic materials such as guanides and quaternaryammonium compounds as well as non-cationic compound8 such as halogenated l~alicylanilides and halogenated hydroxydiphenyl ether6.
!! Hitherto, the cstionic antibacterial materials such as ! chlorhexldine, benzthonium chloride and cetyl pyridinium chloride have been the sub~ect of greatest lnvestlgation as antlbacterial antiplaque agents. However, in spite of thelr being used in con~uction with zinc ~anticalculus agent, they are not effective when used wlth anionlc i!materials such as polyphosphate anticalculus agent. Thls ineffectiveness is considered to be qu~te surprising as polyphosphates ; are chelating agents and the chelating effect has previously been known l! to increase the efficacy of catlonlc antlbacterial agent6.(see e.g.
,IDisinfection, Sterlllzatlon and Preservation, 2nd Ed., Black. 1977, page 915 and Inhibition nd De6truction of the Microblal Cell, Hugo, 1971, page 215). Indeed, quaternary ammonium compound is pre6ent ln the plaque control ~outhwash contalnlng pyropho6phate of V.S. Patent ¦4,323,551 and bls-blguanlde antiplaque agent i8 suggested in the antlcalculus pyrophosphate oral compositlon of U.S. Patent 4,515,772.
¦¦ In vlew of the surprlslng lncompatlblllty of cationlc antlbacterlal agent6 wlth polyphosphates present as antlca}culus agents, ¦~
it was quite unexpected that other antlbacterial agent would be effectlve.
It is an advantage of this invention that certaln antibacterlal agents are effective ln antlcalculus oral composltlons to lnhlbit plaque formation i It 18 a further advantage of thls lnventlon that a compo61*ion ¦ls provided which 18 effectlve to reduce plaque and calculus formatlon.
It 18 a further advantage of thls lnvention that an antiplaque, ¦!anticalculus oral composition is provlded whlch 18 effectlve to reduce the occurence of glnglvltls.
li i il : ~ :
1 3 2 7 9 ~ 2 .
. - .: .
Additional advantages of this invention will be . ~ . .
apparent from consideration of the following specification.
In accordance with certain of its aspects this invention relates to an oral composition comprising ln an orally acceptable vehicle, an effective anticalculus amount of material comprising at least one linear molecularly dehydrated polyphosphate salt as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, benzoate esters, and halogenated carbanilides.
The present invention provides an oral composition ccmprising in an orally acceptable vehicle, an effectlve anticalculu~ amount of at least one water-soluble llnear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a ~--, : - :: -substantlally water-insoluble non-cationic antibacterial compound as essential antiplaque agent and about 0.05% to ~-~
about 3% of a water-soluble synthetic anionic polymeric - -~ - :::
polycarboxylate having a molecular weight of about 1,000 to about 1,000,000.
The present invention also provides an oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble ;~
linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, and effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent and.
A~ about 0.05% to about 3% of a water-soluble synthetic anlonic polymeric polycarboxylate; or - 4 _ ,~
i , .
,' '' B) mixtures of A) and an amount Gf a fluoride ion-providing source sufflclent to supply about 25 ppm to about 2,000 ppm of fluoride ions.
The present invention further provides an oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective :
anticalculus amount of at leaæt one water-soluble linear molecularly dehydrated polyphosphate salt a~ essential anticalculuæ agent, an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial : :
compound as es~ential antiplaque agent and:
A) about 0.05% to about 3% of a water-soluble synthetic ~
anionic polymeric polycarboxylate; or : :
B) mlxtures of A) and an amount of a fluoride ion-: providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions. -~
: These oral compositions are useful to combat calculus I and plaque in a mammal. .
j 20 Typical examples of antibacterial agents which are : particularly desirable from considerations of antiplaque effectiveness, safety and formulation are, Haloaenated Dihenvl Ethers 2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan~
2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenolic Com~ounds (including phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorclnol and lts derivatlves and bisphenolic compounds) 'i ; ~ :' ~
1 :
i *Trade-mark - 4a -~ ~ 13279~2 . .
~ 62301-1461 .. ~' :' ~ ,.
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: Phenol and its Homoloqs Phenol 2 Methyl - Phenol 3 Methyl - Phenol 4 Methyl - Phenol 4 ~thyl - Phenol 2,4-Dimethyl - Phenol 2,5-Dimethyl - Phenol 3,4-Dimethyl - Phenol ' ~ "; , ', : ~ '' ' .' "
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1 3 2 ~ ~ ~ 2 :-- 11! 1 2,6-Dimethyl - Phenol 4-n-Propyl - Phenol ,!4-n-Butyl - Phenol 4-n-Amyl - Phenol 4-tert-Amyl - Phenol -n-Nexyl - Phenol 4-n-Heptyl - Phenol iI Mono- and Poly-Alkyl and Aromatic Halophenol6 j!Methyl - p-Chlorophenol Ethyl - p-Chlorophenol !'in-Propyl - p-Chlorophenol n-Butyl - p-Chlorophenol lln-Amyl - p-Chlorophenol ¦
'!sec-Amyl - p-Chlorophenol ~n-Hexyl - p-Chlorophenol ICyclohexyl - p-Chlorophenol 'In-Heptyl - p-Chlorophenol ~n-~ctyl - p-Chlorophenol ! ¦O-Chlorophenol IMethyl - o-Chlo~ophenol jlEthyl - o-Chlorophenol .
'n-Propyl - o-Chlorophenol I ~!n-Butyl - o-Chlorophenol - o-Chlorophenol tert-Amyl - o-Chlorophenol n-Htxyl - o-Chlorophenol ~-Heptyl - o-Chlorophenol ip Chlorophenol o-Benzyl - p-Chlorophenol ,1 ' , i! 1 jl : I 1 ~ ~ 7 :: I
I o-Benzyl-m-methyl - p-Chlorophenol i!o-Benzyl-m, m-dimethyl - p-Chlorophenol ¦¦o-Phenylethyl - p-Chlorophenol o-Phenylethyl-m-methyl - p-Chlorophenol ¦3-Methyl - p-Chlorophenol 3,5-Dimethyl - p-Chlorophenol 6-~thyl-3-methyl - p-Chlorophenol 6-n-Propyl-3-methyl - p-Chlorophenol ~¦6-ico-Propyl-3-methyl - p-Chlorophenol 12-Ethyl-3,5-dimethyl - p-Chlorophenol ,16-sec Butyl-3-methyl - p-Chlorophenol 112-iso-Propyl-3,5-dimethyl - p-Chlorophenol ,j6-Dlethylmethyl-3-methyl - p-Chlorophenol 6-iso-Propyl-2-ethyl-3-methyl - p-Chlorophenol 112-sec Amyl-3,5-dimethyl - p-Chlorophenol ¦i2-Diethylmethyl-3.5-dimethyl - p-Chlorophenol ! 16-sec Octyl-3-methyl - p-Chlorophenol ' ! p-Bromophenol ¦¦Methyl - p-Bromophenol Ethyl - p-Bromophenol n-Propyl - p-Bromophenol I¦n-Butyl - p-Bromophenol ¦¦n-Amyl - p-Bromophenol ¦sec-Amyl ~ p-Bromophenol i!n-Hexyl - p-Bromophenol .,cycl~hexyl - p-Bromophenol o-Bromophenol lltert-Amyl - o-Bromophenol jln-Hexyl - o-Bromophenol .' , .
~: 1 1327~2 ,n-Propyl-m,m-Dimethyl - o-Bromophenol .l2-Phenyl Phenol i,4-chloro-2-methyl phenol 4-chloro-3-methyl phenol j4-chloro-3,5-dlmethyl phenol 2,4-dichloro-3,5-dlmethylphenol ,3,4,5,6-terabromo-2-methylphenol 5-methyl-2-pentylphenol .l4-lsopropyl-3-methylphenol ~S-chloro-2-hydr~xydiphenyhn~Ene Resorcinol and its Derivatives ,Resorcinol 1 ~-:
iMethyl - Resorclnol Ethyl - Resorclnol j~
n-Propyl - Resorclnol ¦
n-Butyl - Resorcinol n-Anyl - Resorclnol n-Hexyl - Resorclnol ¦n-Heptyl - Resorclnol n-Octyl - Resorcinol ¦ I
j¦n-Nonyl - Resorclnol .!Phenyl - Regorclnol Benzyl - Resorclnol Phenylethyl - Resorclnol I :~
Phenylpropyl - Resorclnol p-Chl~robenzyl - Resorclnol 5-Chloro -2,4-Dihydroxydiphenyl Methane 3 !! 4'-Chloro -2,4-Dihydroxydiphenyl Methane ¦¦5-Bromo -2,4-Dihydroxydiphenyl Methane i!
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` . :' ,' 1327~2 4'-Bromo-2,4-Dihydroxydiphenyl Methane Bis~henolic ComPounds 2,2'-methylene bis (4-chlorophenol) 2,2'-~ethylene bis (3,4,6-trichlorophenol) 2,2'-methylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide. :~
Benzoic Esters p-Hydroxybenzoic Acid Methyl - p-Hydroxybenzoic Acid Ethyl - p-Hydroxybenzoic Acid : - , Propyl - p-Hydroxybenzoic Acid Butyl - p-Hydroxybenzoic Acid Haloaenated Carbanilides :~ `
3,4,4'-trlchlorocarbanllide :~
. ,". ~
3-trifluoromethyl-4,4'-dichlorocarbanilide 3,3',4-trichlorocarbanilide 1~ :
The antlbacterial agent is present in the oral composition in an effective antiplaque amount, typiaally about ~
0.01-5% by welght, preferably about 0.03-1%. The antibacterial ~ `
I agent i8 substantlally water-insoluble, meaning that its i solubility is less than about 1% by weight in water at 25C and ¦ may be even less than about 0.1%. If anionizable group is present solubility is determined at a pH at which ionization does not occur.
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- 13279~2 The preferred halogenated diphenyl ether is Triclosan*. The preferred phenolic compounds are hexyl resor-cinol and 2,2'-methylene bis(4-chloro-6-bromophenol). The most preferred antibacterial antiplaque compound is Triclosan.
Triclosan is disclosed in aforementioned United States Patent 4,022,880 as an antibacterial agent in combination with an anticalculus agent which provides zinc ions. It is also dis-closed as an antiplaque agent in a dentifrice formulated to contain a lamellar liquid crystal surfactant phase having a lamellar spacing of less than 6.0 mm and which may optionally contain a zinc salt in published European Patent application 0161898 of Lane et al and in a dentifrice containing zinc citrate trihydrate in published European Patent Application 0161899 to Saxton.
The linear molecularly dehydrated polyphosphate salts operative herein as anticalculus agent are well known, being generally employed ln the form of their wholly or partially ~-- neutralized water soluble alkali metal ~e.g. potassium and preferable sodium) or ammonium salts, and any mixtures thereof.
Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates and the like. Linear polyphos-phates ~orrespond to (NaPO3)n where n is about 2 to about 125.
They are generally employed in the instant oral compositions in approximate weight amounts of 0.1 to 7% preferably 0.1 to 7%, - -more preferably 2 to 7%. When n is at least 3 in (NaPO3)n, said polyphosphates are glassy in character.
j *Trade Mark _ g -~ ...... ,.. ,.............. ~
13279~2 623~1-1461 Particularly desirable anticalculus agents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetrasodium pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. An anticalculus agent comprising about ~-~
4.3% to about 7% by weight of the oral compositions wherein the weight ratio of tetrapotassium pyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 to about 6:1 is especially preferred.
In order to optimize the anticalculus effectiveness of the oral composition, lnhibitors against enzymatic hydrolysis of the polyphosphate are deslrably present. Such agents are an amount of a fluoride ion source sufficient to supply 25 ppm. to 5,000 ppm. of fluoride ions, and 0% to 3% of a synthetic anionlc polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000, preferably about 30,000 to about 500,000.
The sources of fluoride ions, or fluorine-providing component, as acid phosphaease and pyrophosphatase enzyme inhibitor component, are well known in the art as anti-caries agents. These compounds may be slightly soluble in water or may be fully water-soluble. They are characterized by their ability to release fluoride ions in water and by freedom from undesired reaction with other compounds of the oral preparation. Among these materlals are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium f luoride, a copper f luoride such as cuprous f luorlde, zinc f luoride, barlum f luoride, sodium fluoroslllcate, ammonium fluorosilicate, sodlum fluorozirconate, sodium fluorozlrconate, sodlum K - -- ~
. .
1327~2 ~- 62301-1461 monofluorophosphate, aluminum mono- and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as ~odium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.
~;. ~'' ~ - lOa -The amount of fluorine-providing compound is dependent to some extent upon the type of compound, its solublllty, and the type or oral preparatlon, but it must be a non-toxlc amount, generally abut 0.005 to about 3.0% in the preparation. In a dentifrice preparationr e.g. dental gel, toothpaste (including cream), toothpowder, or dental tablet, an -amount of such compound which releases up to about 5,000 ppm of F ion by weight of the preparation is considered satisfactory. :
Any suitable minimum amount of such compound may be used, but it is preferable to employ sufficient compound to release about 300 or, preferably 1085, to 2,000 ppm. more preferable about ~ ~;
800 to about 1,500 ppm of fluoride ion. ;~
~ypically, in the cases of alkali metal fluorides, this component is present in an amount up to about 2~ by weight, ba~ed on the welght of the preparation, and preferably in the range of about 0.05% to 1%, particularly in excess of 0.22%. In the case of sodiu~ monofluorophosphate, the compound may be present in an amount of about 0.1-3%, more typically about 0.76%, preferably ln excess of 0.80%.
In dentlfrice preparations such as lozenges and chewlng gum, the fluorlne-provlding compound i8 typlcally present ln an amount sufflclent to release up to about 500 ppm, ¦ preferably about 25 to 300 ppm by weight of fluoride lon.
I Generally about 0.005 to about 1.0 wt.~ of such compound ls ¦ present.
The synthetic anlonic polymerlc polycarboxylate is an inhibitor of alkaline phosphata~e enzyme. Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zlnc and magneslum have been prevlou~ly dlsclo~ed as anticalculus agent# per se in, for example U.S.
Patent No. 3,429,963 to Shedlovsky; U.S. Patent No. 4,152,420 ;~
',Cj - 11-:
13~7~2 to Gaffar; U.S. Patent No. 3,956,480 to Dichter et al; U.S.
Patent 4,138,477 to Gaffar; and U.S. Patent No. 4,183,914 to Gaffar et al. However, only in aforementioned U.S. Patent 4,627,977 to Gaffar et al i8 there dlsclosed use of such polycarboxylates alone for inhibiting salivary hydrolysis of pyrophosphate anticalculus agents, much less in combination with a compound providing a source of fluoride ion. It is to be understood that the synthetic anionic polymeric polycarboxylates so disclosed in these several patents are operative in the compositions and methods of this invention. ~ ~-The synthetic anionic polymeric polycarboxylates optionally but preferably employed herein are, as indicated above, well known, being often employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble alkali metal (e.g. potassium and preferably sodium) or ammonium salts. Preferred are 1 t 4 to 4 copolymers of maleic anhydride or acid with another polymerlzable ethylenically unsaturated monomer, preferably methyl vinyl ether (maleic anhydride) having a molecular weight -(M.W.) of about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez* (AN 139 (M.W. 500,000), A.N. 119 (M.W. 250,000); and preferably S-97 Pharmaceutical Grade (H.W. 70,000), of GAF Corporation. The term "synthetic"
is intended to exclude known thickening or gelling agents comprising carboxymethylcellulose and other derlvatives of cellulose and natural gums.
Other operative polymeric polycarboxylate~ include those disclosed in U.S. Patent No. 3,956,480 referred to above, such as the 1-1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto*
~ *Trade-mark - 12 -, ::
1 3 2 7 ~ ~ 2 EMA No. 1103*, N.W. 10,000 and EMA Grade 61~, and 1~
copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidine. ~.
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,, ~
;; ~ *Trade-mark - 12a - ~
` ll 1327942 Additional operative polymeric polycarboxylate6 dlsclosed in above referred to V.S. Patent No. 4,138,477 and 4,183,914, lnclude copolymers of maleic snhydrlde with styrene, isobutylene or ethyl vinyl ¦ether, polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylic lollgomers of M.W. a8 low ag 1,000, available as Uniroyal ND-2.
l Suitable generally are polymerized olefinically or ¦
~ lellically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, ,~hat is, an acid containing an olefinic double bond which readily functions in polymerization because of its pre6ence in the monomer molecule either in the alpha-beta posltion with respect to a carboxyl ii i group or as part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, ¦crotonlc, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic, ibeta-styrilacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic~ aconitic, alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angellc, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomer6 include vlnylacetate, vinyl chloride, dimethyl ¦
maleate and the like. Copolymers contain sufficient carboxylic salt ¦groups for water-solubility.
¦ A180 useful herein are so-called carboxyvinyl polymers disclosed as toothpaste components in Urs~ 3,980,767 to Chown et al;
U~ 3,935,306 to Robert6 et al; U.S. 3,919,409 to Perla et al; U.S.
3,911,904 to Harrison, and U.S. 3,711,604 to Colodney et al. They are ccmmercially available for example under the trademarks Carbopol 934, 19~0 and 941 of B. F. Goodrich, these products consisting essentially of lla colloidally water-60luble polymer of polyacrylic acid crossllnked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent.
''I . ' li '.
Il -13-- ~ 71 ~ !~
13279~2 1 :
; lne synthetlc anionlc polymerlc polycarboxylate component 18 ~malnly a hydrocarbon ~l~h optional halogen and O-contalnlng substltuents ¦
and llnkages as present ln for example ester, ether and OH group6, and 'iwhen pregent 18 generally employed ln the lnstsnt composltlons in I approximate welght amounts of 0.05 to 3X, preferably 0.05 to 2X, more preferably 0.1 to 2%. Amounts ln the upper portlons of these ranges are typl-ally employed ln dentlfrlce composltlons typlcally contalnlng a 'dental abraslve and used ln con~unctlon wlth brushing of the teeth, e.g. ', itooth pastes (lncludlng creams), gels, powders and tablets. ~mounts ln iexcess of these ranges may be employed for thlckenlng or gelllng ! j purposes.
I i As lndicated above, these polymerlc polycarboxylates have been ~found to be effective lnhlbltors of alkallne phosphatase enzyme. Slnce thls enzyme has little actlvlty (for hydrolyzlng pyrophosphate) at about pH 7.0 or below, the poly~erlc polycarboxylate component may, lf desired, be omltted from oral preparatlons formulated to operate at such pH of 7.0 or below. Such omlsslon however could reduce the versatlllty !'and antlcalculus effectlveness of the present oral composltions over the i, I
iibroad pH range of nbout 4.5 to about lO.
In oral preparatIons such as mouthwashes, lozenges and chewing ¦
11 gum, the fluorlne-provldlng compound may be typlcally present ln an iianount sufflclent to release up to about 500 ppm, preferably about 25 to ijabout 300 ppm by welght of fluorlde ion. Generally about 0.005 to about ijl-O wt.X of such compound is present.
, In certaln hlghly preferred forms of the invention the oral compOsltlon may be substantially llquld ln character, such as a mouthwa6h or rlnse. In such a preparatlon the vehlcle 18 typlcally a water-alcohol mlxture deslrably lncludlng a humectant as descrlbed below. Generally, the welght ratlo of water to alcohol 18 ln the range " !
" ' :
1l -14-327~2 ol from about l:1 to aDout 20:1, preferably about 3:1 to lO:l and more ~preferably about 4:1 to about 6:i. The totai amount of water-alcohol ¦mlxture ln this type of preparatlon ls typlcally ln the range of from ! about 70 to about 99.9X by weight of the prepar~tlon. The alcohol 18 ltypically ethanol or isopropanol. Ethanol is preferred.
¦ The pH of such llquid and other preparatlons of the inventlon iis generally ln the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pH 18 preferably ln the range of from about 6 ¦to about 8Ø It 18 noteworthy that the composltlons of the lnvention jmay be applled orally at a pH below 5 wlthout substantlally decalclfying !1 or otherwise damaglng dentsl enamel. The pH can be controlled wlth acld (e.g. cltrlc acid or benzolc acid) or base (e.g. sodlum hydroxlde) or buffered (as wlth sodlum cltrate, benzoate, carbonate, or blcarbonate, !!dlsodlum hydrogen phosphate, sodium dlhydrogen phosphate, etc.).
jj In certaln other deslrable forms of thls lnventlon, the oral ;,composltlon may be substantially solid or pasty ln character, such as ! toothpowder, a dental tablet or a dentlfrlce, that 18 a toothpaste (dental cream) or gel dentifrlce. The vehlcle of such solid or pasty ~oral preparatlons generally contalns dentally acceptable pollshing i material. Examples of pollshlng ~aterials are water-insoluble sodlum metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated alcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, lmagensium orthophosphate, trlmagnesium phosphate, calcium carbonate, ¦alumlnum sll~cate, zlrconium silicate, silica, bentonite, and mixtures Ithereof. Other suitable polishing materlal lnclude the partlculate i! ther~osettlng reslns descrlbed ln U.S. Pat. No. 3,070,510 of Dec. l5, 1962 such aR melamlne-, phenollc, and urea-formaldehydes, and ,cross-llnked polyepoxldes and polyesters. Preferred pollshlng materlals lnclude crystalllne slllca havlng partlcle slzed of up to about 5 l !
,1 , ` 11 -15-'i, ;
. I
'" 11 3279~2 mlcron6~ a mean partlcle 6ize or up tu about 1.1 microns, and a surface area of up to about 50, 000 cm.2/gm., sillca gel or colloidal slllca, I and complex amorphous alkali metal alumlnosllicate.
When vlsually clear gel6 are employed, a poll6hlng agent of colloidal silica, 6uch as those sold under the trademark SYLOID as ¦¦Syloid 72 and Sylold 74 or under the trademark SANTOCEL as Santocel 100 alkali metal almuino-silicate complexes are particularly useful, since Ithey have refractlve lndices close to the refractlve lndlces of gelling ¦jagent-liquld (including water and/or humectant)system6 commonly used in Identifices.
Many of the so-called 'water-insoluble" polishing materials are li i anionic in character and alsv lnclude small a~ounts vf soluble material.
~Thus~ lnsoluble sodlum metaphosphate may be formed in any sultable ¦manner as illustrated by Thorpe's Dlctlonary of Applied Chemlstry, Volume 9, 4th Edltlon, pp. 510-511. The forms of lnsoluble sodlum ,metaphosphate known as Nadrell's salt and Rurrol's salt are further ¦examples of sultable materlals. These metapho6phate salt6 exhiblt only ;la mlnute solubility in water, and therefore are commonly referred to as ¦insoluble metaphosphate6 (IMP). There is present therein a minor amount ¦¦of soluble phosphate material as lmpurltles, usually a few percent such jlas up to 4% by wei8ht. The amount of soluble phosphate materlal, whlch Ills believed to lnclude a soluble sodlum trlmetaphosphate in the case vf ! insoluble metaphosphate~ may be reduced or elimlnated by washlng wlth ~¦water if deslred. The lnsoluble alkall metal metaphosphate ls typlcally employed ln powder form of a partlcle slze such that no more than 1% of ¦
!! the materlal 18 larger than 37 mlcrons.
I The pollshlng materlal ls generally pre6ent ln the solld or Ipasty composltlons ln welght concentratlons of about lOZ to about 99%.
Preferably, lt 18 present in amounts ranging from about lOZ to about 75% ¦
Il I .~
.. ' .'~
ll -16- ~
!
! ~
~: ~: ll 13279~2 'in toothpaste, and from about 700 to about 99% in toothpowder.
! In a toothpaste, the llquid vehicle may comprise water and ¦humectant typically ln an amount ranglng from about IOX to about 80Z by weight of the preparation. Glycerine, propylene glycol, sorbitol, I!polypropylene glycol ant/or polyethylene glycol (e.g. 400-600) exemplify ;Isuitable humectants/carrier6. A180 advantageous are liquit ~ixtures of Iwater, glycerine and sorbitol. In clear gels where the refractive index jis an important con6ideration, about 3-30 wt. % of water, O to about 70 ¦wt.X of glycerine and about 20-80 wt. % of sorbltol are preferably employed.
~! Toothpastes, creams and gels typically contain a natural or l6Ynthetic thickener or gelling agent in proportions of about 0.1 to ¦!about 10, preferably about 0.5 to about 5wt.%. A suitable thickener is l6ynthetic hectorite, a synthetic colloltal magne61um alk li metal ~sllicate complex clay available for example as Laponite (e.g. CP, SP
~i2002,D) marketed by Laporte Industries Limitet. Laponite D analysis show6, approximately by weight, 58.00X SiO2, 25.40X MgO, 3.05Z Na20, .98~ Li20, and some water and trace metals. Its true specific gravity is 2.53 and it has an apparent bulk density (g./ml. at 8% moisture) of ~-o-Other suitable thickeners include Irish moss, gum tragacanth, 'Istarch, polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl ¦ llmethyl cellulo6e, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g. available as Natrosol), sodium carboxymethyl cellulose, and icolloidal silica such as finely ground Syloid (e.g. 244).
It will be understood that, as is conventional, the oral . I
preparations are to be sold or otherwise distributed ln suitable labelled packages. Thus a ~ar of mouthrinse will have a label de6cribing it, in substance, as a mouthrinse or mouthwash and having 1~ r~e-~ I
. i .~, 11 1.
~ !1 13279~2 ,j dlrections for ltæ u~e; and a eoothpaste, cream or gel will u~ually be ¦¦ in ~ collapsible tube, typically aluminum, lined lead or plastic, or other ~queeze, pump or pressurized dlspenser for meterlng out the contents, havlng a label descrlblng it, ln substance, as a toothpaste, j gel or dental cream.
Organic surface-active agents are used in the compositions of the present invention to achieve increased prophylactic action, assist ln achieving thorough and complete dispersion of the anticalculu~ agent ¦ throughout the oral cavity, and render the lnstant compo6itlon6 more cosmetically acceptable. The organic 6urface-active material is preferably anionlc, nonionic or ampholytic In nature, and it i6 !! preferred to employ as the surface-active agent a detersive material !¦ which lmparts to the composition detersive and foaming properties.
Sultable e~camples of anionic ~urfactants are water-soluble salts of ¦higher fatty acld monoglyceride monosulfates, such as the sodium salt of the monosulfatet monoglyceride of hydrogenated coconut oil fatty acids, 1 ~ ¦
'! higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl ~1 sulfonates wch as 60dium dodecyl benzene sulfonate, higher alkyl ulfoacetate6, higher fatty acid esters of 1,2-dihydroxy propane ¦ 6ulfonate, and the substantlally 6aturated higher aliphatic acyl amide6 j¦ of lower aliphatlc amino carboxylic acid compounds, such as those having Il 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the . i i! like. Example~ of the la6t mentioned amide6 are N-lauroyl sarco6ine, .i ' !l and the 60dium, pota66ium, and ethanolamine salt6 of N-lauroyl, . . ~
'i N-myristoyl, or N-palmitoyl sarcosine which should be substsntially free j from 60ap or similar higher fatty acid material. The use of these , ¦
sarcosinate compounds in the oral compositions of the present lnvention partlcularly advantageous since these materlals exhibit n prolonged !! and marked effect ln the inhibition of acid formatlon ln the oral cavlty ~i , 1", `- 1 3 2 7 9 ~ 2 -~ due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydro-phobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydr c alcohols (e.g. sobitan mono-C sterate) and polypropyleneoxide (e.g. Pluronic materials). It is preferred to use from about 0.05 to 5% by weight and preferably about 0.5 to 5% of the foregoing surface active materials in the instant compositions.
Various other materials may be incorporated in the oral prepar-ations of this invention such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated material such as urea, diammonium phosphate, and mixtures thereof.- These adjuvants, where present, are incorporated in the preparations in amounts which do not substantially adversely affect the properties and characteristics desired. Significant amounts of ~inc, magnesium and other metal salts and materials, generally soluble, which would complex with active components of the instant invention are to be avoided.
Any suitable flavoring or sweetening material may also be employed.
Examples of suitable flavoring constituents are flavoring oils, e.g. oil of spearmint, peperment, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon~ and orange~ and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitil, xylitol, sodium cyclamate, perillartine, AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.1% to 5% more of the preparation.
In the preferred practice of this invention an oral composition ~ I ra~
:
l! I
~ ;l 13279~2 1l!
~according to this lnvention such as a mouthwash or den~ifrlce contalning ithe composition of the present inventlon i6 preferably applied regularly to dentsl enamel, such as every day or every second or third day or preferably from 1 to 3 tlmes daily, at a pH of about 4.5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up to llfetime.
The compositions of this lnvention can be incorporated in lozenges, or in chewing gum or other products, e.g. by stirring into a warm gum base or coating the outer surface of a gum bage, illustrative ' of which may be mentioned ~elutone, rubber latex, vinylite resins, etc., I
, desirably with conventional plasticizers or softeners, sugar or other ~ ~j ;i Isweeteners or carbohydrates such as glucose, sorbitol and the like.
j The following examples are further illu~trative of the nature ' ! of the present lnvention, but it is under~tood that the invention 18 not ,limited thereto. All amounts and proportlons referred to herein and in the appended claims are by welght. ¦
., I ,,~.
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~, . i 1~27942 E~ample I
¦¦ Slurries and golutions tescrlbed below are prepared to determine ~effectiveness ln terms of minlmum lnhlb~tory concentratlon (MIC) of ~¦various antlbacterlal agents agalnst a variety of oral bacterlal organisms lmpllcated in format$on of plaque and leadlng to glngivitl6 on dental surfaces. Soft plaque contalns about 1.7 x 101l organism/gm.
(net weight). The antibacterlal agents are admlxed wlth anlonlc materlals, partlcularly anlonic surface actlve agent often commonly employed in oral composltlons and polyphosphate antlcalculus agent.
Minimum inhlbitory concentratlon (MIC) of antlbacterial agent ¦
jls used to evaluate the efficacy of the agent ln vltro. MIC is deflned ;~as the mlnlmum concentratlon ln mlcrograms/ml of antlbacterlal agent at ¦whlch the growth of bacterla 18 completely lnhlblted by the agent. The ;smaller the MIC value the greater is the efficacy of the antlbacterlal ! agent to lnhlblt the growth of the bacterla. The ln vltro MIC data 18 'Ir~lated to the efflcacy of the dentlfrlce ln vlvo slnce retentlon and release of antlbacterlal agent lnto the oral cavlty after toothbrushlng i8 ln the range of mcg/ml-¦¦ In the Tables, followlng dlsclosure and following E~amples, the agent Trlclosan, 2,4,4'-trlchloro-2'-hytroxydlphenyl ether 18 lndlcated I!as "TCHE"; the quaternary ammonlum antlbacterlal agents benzthonlum !
ilchlorlde 18 lndlcated a6 BTC ; The blguanlde chlorhexldlne dlgluconate ¦
ls lndlcated as "CH , sodlum lauryl sulfate 18 lndlcated as SLSn; the copclymer of malelc anhydrlde and methyl vlnyl ether avallable from GAF
i!corporatlon as "Gantrez S-97" is identifled as "Gantrezn; tetrasodium i! pyrophosphate 18 identifled as "pyrophosphate ; and sodlum fluorlde ls l! ldentlfled as "~aF".
~1 !
~ -21- !
Il . i, Il ji il ,1 13279~2 li TABLE 1 Il .
I Minlmum Inhlbltlon Concentratlon Test (MIC) ISolutlon ln mcg/ml ,j Bacterlode~ Bacterlodes Actlnobaclllus Streptococcu6 glnglvall6 lntermedlus actlnomycetem- mutanR
comitans jl. 0.5% TCHE and 2.5 2.5 5.0 25.0 , l~ SLS ln ! water j~2. 0.5% TCHE, 2.5 2.5 5.0 25.0 i lX SLS, ! I% Gaotrez, l 2X Pyrophosphate I and 0.2% NaF ln ! water l3- 1% SLS in NE NE NE NE
!i water 4. lX SLS, NE NE NE NE
lX Gantrez and 2X Pyrophosphate ll in water ¦¦note: NE ~ not effectlve .I , , j The regults lndlc-te that TCHE ln the presence of anlonlc surfactant lnhlbltet four dental plsque organlsms, Bacteriodes glngivalis, Bacterolte~ lntermedlus, Actlnobaclllus - -actlnomyretemcomlt-ns and Strep. DDe-D~ at 2.5 mcg/ml and 2.5 ~cg/ml, ~1 15.o mcg/ml and 25.0 mcg/ml re~pectively(I). Slmilar antlbacterlal effect i8 seen ln the presence of Gantrez/pyrophosphate/fluoride(2).
i SLS per se and a combination of SLS/Gantrez/pyrophosphate/fluoride wa~
;~ ineffectlve(3 ant 4).
It i8 noteworthy that in human clinical tests with cationic antibacterial agents, 0.075% BTC dissolved in water is effective ln ¦reducing plaque formation while 0.075~ BTC and 1~ pyrosphosphate ~!dissolved in water is not. Simil-rly, O.OlX CH dissolved in water is ¦effective in retuclng plaque formation while 0.01% CH and 1% sotium N-lauroyl ~arcosinate dissolved in water 18 not.
!!
~ I -22-, I
11 13279~2 !l I
'' Example 2 ,, The adsorption to and release from tooth mineral6 for sntiplaque/ ~ntltartar efflcacy of agents is assesset by atsorptlon of an~ibacterial agent to saliva coated tooth mineral hydroxyapatite ln the presence ant the absence of pyrophosphate (soluble tetrasodlum pyroph~sphate)tGantrez/NaF.
200 mg. of hydroxyapatlte (HA) is treated with human ~aliva for 2 hours. The excess saliva 18 washed off with a buffer and saIiva coated HA
is used for adsorption studies. Variou~ concentratlons of TCHE in SLS
~or in SLS/pyrophosphate/Gantrez/NaF are mixed with the coated HA and lnc~bated at 37 for 3 hours under continuous agitation. At the end of iincubation period, the mixture6 are centrifuged, HA separatet and the ij amounts of TCHE adsorbed determined by estimating TCHE in the 'Isupernatant at 283nM in a Gilford spectrophotometer. The amounts l~¦adsorbed are calculated by the difference between the amount added and j¦the amount left ln the supernatant after the lncubation with coated HA.
The table below summarizes the data.
1l 1 .i . ' '. ,i , I
,, 1 ;~ jj i l! I
Il -23-i 3;27~2 I, TABLE 2 Il I , ~'Co~eonents and Concentratlons % of TCHE Adsorbed to Coated HA
.5Z TCHE ln lX SLS 80X
O.OIX TCHE in 1% SLS 85%
j0.015Z TCHE in 1~ SLS 85%
0.02X TCHE ln lZ SLS 88%
0.005% TCHE ln lX SLS; 0.5% 80%
Gantrez, 2X pyrophosphate/ ! ::
0.24X NaF
'IO~OlX TCHE ~ 85X
:, I :'"' ;,0.015X TCHE " 86X I -~
0.02Z TCHE " 87%
ll The tata lndlcates that the addltlon of pyrophosphate/
i I I
Gantrez/NaF does not lmpalr adsorption of TCHE to sallva coated tooth ~minerals.
,, i ! i -1! I
!¦ l i j 1 , 1.
,1 , 1~ -24-: :~
: :
Example 3 ¦iDentlfrice Composltlons A B C
Parts Parts Parts Glycerine 15.00 10.20 15.00 ¦Polyethylene Glycol 600 5.00 3.00 5.00 ,lv~a Carrageenan 0.60 - 0.60 ISodium Carboxymethyl Cellulose - 1-00 Sodlum Saccharin 0.40 - 0.40 ,,Sodlum Cyclamate - 3.00 - I ~:
j;Sodium Fluoride 0.243 0.243 0.243 .. I
Deionlzed water 15.08 29.907 23.657 Titanlum Dio~ite - - 0.50 lsodlum Benzoate - 0.50 ~iFD&C Blue No. 1(1% Solutlon) 0.400 : j,Sorbltol (70~) 19.807 22.50 22.50 ~ Gantrez S-97 8.330t*) 1.00(**) 1.00(**) 1 :
; IjTetrasotlum Pyrophosphate1.50 1.50 1.50 : ¦!Tetrapotasslum Pyrophosphate 4.50 4.50 4.50 Preclphatet Amorph. Hydrated Silica 16.00 19.50 ~ IIPreciphated Amorp. Silica - - 16.00 7 ¦i containing combined alu~ina i : ,jSllica Thickener 7.00 - 5.50 jjFlavor 1.10 0.95 1.10 otlum Lauryl Sulfate 1.20 1.20 1.20 3~ iiTCHE 0 50 0 50 0.50 * liquld '!** powter '~ il I
~ ! i ,';
~ -25-1~27~2 Example 4 The dentifrlce descrlbed ln Example 3A 16 compared with the ~ame compositlon except without any TCHE and wlth added 0.50 parts of vater. Aqueous extracts of each dentlfrlce are prepared as follows: 50 ml of dlstllled water i8 added to 1.0 gm of each déntlfrlce, mlxed well for a couple of hours with stlrrlng bar and centrifuged, after which the ~upernatant i6 collected as aqueous extract. Antlbacterlal actlvlty of ;~
the dentifrlce extracts are evaluated on Bacterlodes gingivalls. -;~
Results are summarized below.
TA8~E 3 Inhlbltion of Growth of Bacterlodes Glnglvalls Tr~at~ent ~ _ Extract from dentifrice contalnlng 100.0 TCHE (1:500) Extract from dentlfrlce wlthout 0.0 TCHE (1:509) TCHE (5.0 mcg/ml) by itself 100.0 '-Ihese results lndlcate that TCHE antlbacterlal antlplaque agent is compatible ln a dentifrice composltion contalnlng anlonic surfactant plus pyrophosphate antlcalculus lngredients wlth enzyme inhibltors Cantrez and NaF. Simllar comparable effects prevall when each of hexyl resorcinol, 2,2'-methylene bls~4-chloro-6-bromophenol)/
replace TCHE.
, .
.~ .
.
13279'12 j ~xample 5 M uthrinse Part_ Tetrasodium Pyropho6phate 2.00 ~!Gantrez S-97 0.25 j¦Glycerine 10.00 ¦¦Sodlum Fluoride 0.05 Pluronic* F108 2.00 - (Polyoxyethylene/Polyoxypropylene Block Copolymer) ITCHE o.lo Flavor 0.40 ~!water Q.S. to 100.00 Example 6 Lozenge 75-80% Sugar 20% Corn Syrup ,10.1-1.0 Flavor 2% Tetrasodium Pyrophosphate ji0.25X Gantrez S-97 '0.01 to 0.05X NaF
¦¦0.01 to O.lZ TCHE
1 to 5X Magne6ium Stearate Lubricant ',0.01 to 0.2Z Water ! *Trade Mark !
1, l!
jj I!
i.l ! Examnle 7 r ;l I
Chewing Gum Parts ! Gum base 25.00 . Sorbltol (70X) 17.00 TCHE 0.50 to 0.10 Tetrasodium Pyrophosophate 2.00 Gantrez S.97 0.25 ,NaF 0 05 ~Glycerine o.5o ICrystalline Sorbitol 53.00 " Flavor and Water Q.S. to 100.00 This invention has been described wlth respect to certain ¦preferred embodiments and it will be understood that modifications and .jvariations thereof obvious to those skilled ln the art are to be lincluded within the purview of this application and the scope of the j! appended claims.
!l Il I
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1 3 2 7 9 ~ 2 compounds includ .g cationic materials such as guanides and quaternaryammonium compounds as well as non-cationic compound8 such as halogenated l~alicylanilides and halogenated hydroxydiphenyl ether6.
!! Hitherto, the cstionic antibacterial materials such as ! chlorhexldine, benzthonium chloride and cetyl pyridinium chloride have been the sub~ect of greatest lnvestlgation as antlbacterial antiplaque agents. However, in spite of thelr being used in con~uction with zinc ~anticalculus agent, they are not effective when used wlth anionlc i!materials such as polyphosphate anticalculus agent. Thls ineffectiveness is considered to be qu~te surprising as polyphosphates ; are chelating agents and the chelating effect has previously been known l! to increase the efficacy of catlonlc antlbacterial agent6.(see e.g.
,IDisinfection, Sterlllzatlon and Preservation, 2nd Ed., Black. 1977, page 915 and Inhibition nd De6truction of the Microblal Cell, Hugo, 1971, page 215). Indeed, quaternary ammonium compound is pre6ent ln the plaque control ~outhwash contalnlng pyropho6phate of V.S. Patent ¦4,323,551 and bls-blguanlde antiplaque agent i8 suggested in the antlcalculus pyrophosphate oral compositlon of U.S. Patent 4,515,772.
¦¦ In vlew of the surprlslng lncompatlblllty of cationlc antlbacterlal agent6 wlth polyphosphates present as antlca}culus agents, ¦~
it was quite unexpected that other antlbacterial agent would be effectlve.
It is an advantage of this invention that certaln antibacterlal agents are effective ln antlcalculus oral composltlons to lnhlbit plaque formation i It 18 a further advantage of thls lnventlon that a compo61*ion ¦ls provided which 18 effectlve to reduce plaque and calculus formatlon.
It 18 a further advantage of thls lnvention that an antiplaque, ¦!anticalculus oral composition is provlded whlch 18 effectlve to reduce the occurence of glnglvltls.
li i il : ~ :
1 3 2 7 9 ~ 2 .
. - .: .
Additional advantages of this invention will be . ~ . .
apparent from consideration of the following specification.
In accordance with certain of its aspects this invention relates to an oral composition comprising ln an orally acceptable vehicle, an effective anticalculus amount of material comprising at least one linear molecularly dehydrated polyphosphate salt as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, benzoate esters, and halogenated carbanilides.
The present invention provides an oral composition ccmprising in an orally acceptable vehicle, an effectlve anticalculu~ amount of at least one water-soluble llnear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a ~--, : - :: -substantlally water-insoluble non-cationic antibacterial compound as essential antiplaque agent and about 0.05% to ~-~
about 3% of a water-soluble synthetic anionic polymeric - -~ - :::
polycarboxylate having a molecular weight of about 1,000 to about 1,000,000.
The present invention also provides an oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble ;~
linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, and effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent and.
A~ about 0.05% to about 3% of a water-soluble synthetic anlonic polymeric polycarboxylate; or - 4 _ ,~
i , .
,' '' B) mixtures of A) and an amount Gf a fluoride ion-providing source sufflclent to supply about 25 ppm to about 2,000 ppm of fluoride ions.
The present invention further provides an oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective :
anticalculus amount of at leaæt one water-soluble linear molecularly dehydrated polyphosphate salt a~ essential anticalculuæ agent, an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial : :
compound as es~ential antiplaque agent and:
A) about 0.05% to about 3% of a water-soluble synthetic ~
anionic polymeric polycarboxylate; or : :
B) mlxtures of A) and an amount of a fluoride ion-: providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions. -~
: These oral compositions are useful to combat calculus I and plaque in a mammal. .
j 20 Typical examples of antibacterial agents which are : particularly desirable from considerations of antiplaque effectiveness, safety and formulation are, Haloaenated Dihenvl Ethers 2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan~
2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenolic Com~ounds (including phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorclnol and lts derivatlves and bisphenolic compounds) 'i ; ~ :' ~
1 :
i *Trade-mark - 4a -~ ~ 13279~2 . .
~ 62301-1461 .. ~' :' ~ ,.
... .
.:
: Phenol and its Homoloqs Phenol 2 Methyl - Phenol 3 Methyl - Phenol 4 Methyl - Phenol 4 ~thyl - Phenol 2,4-Dimethyl - Phenol 2,5-Dimethyl - Phenol 3,4-Dimethyl - Phenol ' ~ "; , ', : ~ '' ' .' "
~:~ :`:
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~: .
,~ :
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1 3 2 ~ ~ ~ 2 :-- 11! 1 2,6-Dimethyl - Phenol 4-n-Propyl - Phenol ,!4-n-Butyl - Phenol 4-n-Amyl - Phenol 4-tert-Amyl - Phenol -n-Nexyl - Phenol 4-n-Heptyl - Phenol iI Mono- and Poly-Alkyl and Aromatic Halophenol6 j!Methyl - p-Chlorophenol Ethyl - p-Chlorophenol !'in-Propyl - p-Chlorophenol n-Butyl - p-Chlorophenol lln-Amyl - p-Chlorophenol ¦
'!sec-Amyl - p-Chlorophenol ~n-Hexyl - p-Chlorophenol ICyclohexyl - p-Chlorophenol 'In-Heptyl - p-Chlorophenol ~n-~ctyl - p-Chlorophenol ! ¦O-Chlorophenol IMethyl - o-Chlo~ophenol jlEthyl - o-Chlorophenol .
'n-Propyl - o-Chlorophenol I ~!n-Butyl - o-Chlorophenol - o-Chlorophenol tert-Amyl - o-Chlorophenol n-Htxyl - o-Chlorophenol ~-Heptyl - o-Chlorophenol ip Chlorophenol o-Benzyl - p-Chlorophenol ,1 ' , i! 1 jl : I 1 ~ ~ 7 :: I
I o-Benzyl-m-methyl - p-Chlorophenol i!o-Benzyl-m, m-dimethyl - p-Chlorophenol ¦¦o-Phenylethyl - p-Chlorophenol o-Phenylethyl-m-methyl - p-Chlorophenol ¦3-Methyl - p-Chlorophenol 3,5-Dimethyl - p-Chlorophenol 6-~thyl-3-methyl - p-Chlorophenol 6-n-Propyl-3-methyl - p-Chlorophenol ~¦6-ico-Propyl-3-methyl - p-Chlorophenol 12-Ethyl-3,5-dimethyl - p-Chlorophenol ,16-sec Butyl-3-methyl - p-Chlorophenol 112-iso-Propyl-3,5-dimethyl - p-Chlorophenol ,j6-Dlethylmethyl-3-methyl - p-Chlorophenol 6-iso-Propyl-2-ethyl-3-methyl - p-Chlorophenol 112-sec Amyl-3,5-dimethyl - p-Chlorophenol ¦i2-Diethylmethyl-3.5-dimethyl - p-Chlorophenol ! 16-sec Octyl-3-methyl - p-Chlorophenol ' ! p-Bromophenol ¦¦Methyl - p-Bromophenol Ethyl - p-Bromophenol n-Propyl - p-Bromophenol I¦n-Butyl - p-Bromophenol ¦¦n-Amyl - p-Bromophenol ¦sec-Amyl ~ p-Bromophenol i!n-Hexyl - p-Bromophenol .,cycl~hexyl - p-Bromophenol o-Bromophenol lltert-Amyl - o-Bromophenol jln-Hexyl - o-Bromophenol .' , .
~: 1 1327~2 ,n-Propyl-m,m-Dimethyl - o-Bromophenol .l2-Phenyl Phenol i,4-chloro-2-methyl phenol 4-chloro-3-methyl phenol j4-chloro-3,5-dlmethyl phenol 2,4-dichloro-3,5-dlmethylphenol ,3,4,5,6-terabromo-2-methylphenol 5-methyl-2-pentylphenol .l4-lsopropyl-3-methylphenol ~S-chloro-2-hydr~xydiphenyhn~Ene Resorcinol and its Derivatives ,Resorcinol 1 ~-:
iMethyl - Resorclnol Ethyl - Resorclnol j~
n-Propyl - Resorclnol ¦
n-Butyl - Resorcinol n-Anyl - Resorclnol n-Hexyl - Resorclnol ¦n-Heptyl - Resorclnol n-Octyl - Resorcinol ¦ I
j¦n-Nonyl - Resorclnol .!Phenyl - Regorclnol Benzyl - Resorclnol Phenylethyl - Resorclnol I :~
Phenylpropyl - Resorclnol p-Chl~robenzyl - Resorclnol 5-Chloro -2,4-Dihydroxydiphenyl Methane 3 !! 4'-Chloro -2,4-Dihydroxydiphenyl Methane ¦¦5-Bromo -2,4-Dihydroxydiphenyl Methane i!
!
,j . i il ~7~
` . :' ,' 1327~2 4'-Bromo-2,4-Dihydroxydiphenyl Methane Bis~henolic ComPounds 2,2'-methylene bis (4-chlorophenol) 2,2'-~ethylene bis (3,4,6-trichlorophenol) 2,2'-methylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide. :~
Benzoic Esters p-Hydroxybenzoic Acid Methyl - p-Hydroxybenzoic Acid Ethyl - p-Hydroxybenzoic Acid : - , Propyl - p-Hydroxybenzoic Acid Butyl - p-Hydroxybenzoic Acid Haloaenated Carbanilides :~ `
3,4,4'-trlchlorocarbanllide :~
. ,". ~
3-trifluoromethyl-4,4'-dichlorocarbanilide 3,3',4-trichlorocarbanilide 1~ :
The antlbacterial agent is present in the oral composition in an effective antiplaque amount, typiaally about ~
0.01-5% by welght, preferably about 0.03-1%. The antibacterial ~ `
I agent i8 substantlally water-insoluble, meaning that its i solubility is less than about 1% by weight in water at 25C and ¦ may be even less than about 0.1%. If anionizable group is present solubility is determined at a pH at which ionization does not occur.
::
~: :
- 13279~2 The preferred halogenated diphenyl ether is Triclosan*. The preferred phenolic compounds are hexyl resor-cinol and 2,2'-methylene bis(4-chloro-6-bromophenol). The most preferred antibacterial antiplaque compound is Triclosan.
Triclosan is disclosed in aforementioned United States Patent 4,022,880 as an antibacterial agent in combination with an anticalculus agent which provides zinc ions. It is also dis-closed as an antiplaque agent in a dentifrice formulated to contain a lamellar liquid crystal surfactant phase having a lamellar spacing of less than 6.0 mm and which may optionally contain a zinc salt in published European Patent application 0161898 of Lane et al and in a dentifrice containing zinc citrate trihydrate in published European Patent Application 0161899 to Saxton.
The linear molecularly dehydrated polyphosphate salts operative herein as anticalculus agent are well known, being generally employed ln the form of their wholly or partially ~-- neutralized water soluble alkali metal ~e.g. potassium and preferable sodium) or ammonium salts, and any mixtures thereof.
Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates and the like. Linear polyphos-phates ~orrespond to (NaPO3)n where n is about 2 to about 125.
They are generally employed in the instant oral compositions in approximate weight amounts of 0.1 to 7% preferably 0.1 to 7%, - -more preferably 2 to 7%. When n is at least 3 in (NaPO3)n, said polyphosphates are glassy in character.
j *Trade Mark _ g -~ ...... ,.. ,.............. ~
13279~2 623~1-1461 Particularly desirable anticalculus agents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetrasodium pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. An anticalculus agent comprising about ~-~
4.3% to about 7% by weight of the oral compositions wherein the weight ratio of tetrapotassium pyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 to about 6:1 is especially preferred.
In order to optimize the anticalculus effectiveness of the oral composition, lnhibitors against enzymatic hydrolysis of the polyphosphate are deslrably present. Such agents are an amount of a fluoride ion source sufficient to supply 25 ppm. to 5,000 ppm. of fluoride ions, and 0% to 3% of a synthetic anionlc polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000, preferably about 30,000 to about 500,000.
The sources of fluoride ions, or fluorine-providing component, as acid phosphaease and pyrophosphatase enzyme inhibitor component, are well known in the art as anti-caries agents. These compounds may be slightly soluble in water or may be fully water-soluble. They are characterized by their ability to release fluoride ions in water and by freedom from undesired reaction with other compounds of the oral preparation. Among these materlals are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium f luoride, a copper f luoride such as cuprous f luorlde, zinc f luoride, barlum f luoride, sodium fluoroslllcate, ammonium fluorosilicate, sodlum fluorozirconate, sodium fluorozlrconate, sodlum K - -- ~
. .
1327~2 ~- 62301-1461 monofluorophosphate, aluminum mono- and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as ~odium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.
~;. ~'' ~ - lOa -The amount of fluorine-providing compound is dependent to some extent upon the type of compound, its solublllty, and the type or oral preparatlon, but it must be a non-toxlc amount, generally abut 0.005 to about 3.0% in the preparation. In a dentifrice preparationr e.g. dental gel, toothpaste (including cream), toothpowder, or dental tablet, an -amount of such compound which releases up to about 5,000 ppm of F ion by weight of the preparation is considered satisfactory. :
Any suitable minimum amount of such compound may be used, but it is preferable to employ sufficient compound to release about 300 or, preferably 1085, to 2,000 ppm. more preferable about ~ ~;
800 to about 1,500 ppm of fluoride ion. ;~
~ypically, in the cases of alkali metal fluorides, this component is present in an amount up to about 2~ by weight, ba~ed on the welght of the preparation, and preferably in the range of about 0.05% to 1%, particularly in excess of 0.22%. In the case of sodiu~ monofluorophosphate, the compound may be present in an amount of about 0.1-3%, more typically about 0.76%, preferably ln excess of 0.80%.
In dentlfrice preparations such as lozenges and chewlng gum, the fluorlne-provlding compound i8 typlcally present ln an amount sufflclent to release up to about 500 ppm, ¦ preferably about 25 to 300 ppm by weight of fluoride lon.
I Generally about 0.005 to about 1.0 wt.~ of such compound ls ¦ present.
The synthetic anlonic polymerlc polycarboxylate is an inhibitor of alkaline phosphata~e enzyme. Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zlnc and magneslum have been prevlou~ly dlsclo~ed as anticalculus agent# per se in, for example U.S.
Patent No. 3,429,963 to Shedlovsky; U.S. Patent No. 4,152,420 ;~
',Cj - 11-:
13~7~2 to Gaffar; U.S. Patent No. 3,956,480 to Dichter et al; U.S.
Patent 4,138,477 to Gaffar; and U.S. Patent No. 4,183,914 to Gaffar et al. However, only in aforementioned U.S. Patent 4,627,977 to Gaffar et al i8 there dlsclosed use of such polycarboxylates alone for inhibiting salivary hydrolysis of pyrophosphate anticalculus agents, much less in combination with a compound providing a source of fluoride ion. It is to be understood that the synthetic anionic polymeric polycarboxylates so disclosed in these several patents are operative in the compositions and methods of this invention. ~ ~-The synthetic anionic polymeric polycarboxylates optionally but preferably employed herein are, as indicated above, well known, being often employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble alkali metal (e.g. potassium and preferably sodium) or ammonium salts. Preferred are 1 t 4 to 4 copolymers of maleic anhydride or acid with another polymerlzable ethylenically unsaturated monomer, preferably methyl vinyl ether (maleic anhydride) having a molecular weight -(M.W.) of about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez* (AN 139 (M.W. 500,000), A.N. 119 (M.W. 250,000); and preferably S-97 Pharmaceutical Grade (H.W. 70,000), of GAF Corporation. The term "synthetic"
is intended to exclude known thickening or gelling agents comprising carboxymethylcellulose and other derlvatives of cellulose and natural gums.
Other operative polymeric polycarboxylate~ include those disclosed in U.S. Patent No. 3,956,480 referred to above, such as the 1-1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto*
~ *Trade-mark - 12 -, ::
1 3 2 7 ~ ~ 2 EMA No. 1103*, N.W. 10,000 and EMA Grade 61~, and 1~
copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidine. ~.
'' ',; ~
,, ~
;; ~ *Trade-mark - 12a - ~
` ll 1327942 Additional operative polymeric polycarboxylate6 dlsclosed in above referred to V.S. Patent No. 4,138,477 and 4,183,914, lnclude copolymers of maleic snhydrlde with styrene, isobutylene or ethyl vinyl ¦ether, polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylic lollgomers of M.W. a8 low ag 1,000, available as Uniroyal ND-2.
l Suitable generally are polymerized olefinically or ¦
~ lellically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, ,~hat is, an acid containing an olefinic double bond which readily functions in polymerization because of its pre6ence in the monomer molecule either in the alpha-beta posltion with respect to a carboxyl ii i group or as part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, ¦crotonlc, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic, ibeta-styrilacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic~ aconitic, alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angellc, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomer6 include vlnylacetate, vinyl chloride, dimethyl ¦
maleate and the like. Copolymers contain sufficient carboxylic salt ¦groups for water-solubility.
¦ A180 useful herein are so-called carboxyvinyl polymers disclosed as toothpaste components in Urs~ 3,980,767 to Chown et al;
U~ 3,935,306 to Robert6 et al; U.S. 3,919,409 to Perla et al; U.S.
3,911,904 to Harrison, and U.S. 3,711,604 to Colodney et al. They are ccmmercially available for example under the trademarks Carbopol 934, 19~0 and 941 of B. F. Goodrich, these products consisting essentially of lla colloidally water-60luble polymer of polyacrylic acid crossllnked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent.
''I . ' li '.
Il -13-- ~ 71 ~ !~
13279~2 1 :
; lne synthetlc anionlc polymerlc polycarboxylate component 18 ~malnly a hydrocarbon ~l~h optional halogen and O-contalnlng substltuents ¦
and llnkages as present ln for example ester, ether and OH group6, and 'iwhen pregent 18 generally employed ln the lnstsnt composltlons in I approximate welght amounts of 0.05 to 3X, preferably 0.05 to 2X, more preferably 0.1 to 2%. Amounts ln the upper portlons of these ranges are typl-ally employed ln dentlfrlce composltlons typlcally contalnlng a 'dental abraslve and used ln con~unctlon wlth brushing of the teeth, e.g. ', itooth pastes (lncludlng creams), gels, powders and tablets. ~mounts ln iexcess of these ranges may be employed for thlckenlng or gelllng ! j purposes.
I i As lndicated above, these polymerlc polycarboxylates have been ~found to be effective lnhlbltors of alkallne phosphatase enzyme. Slnce thls enzyme has little actlvlty (for hydrolyzlng pyrophosphate) at about pH 7.0 or below, the poly~erlc polycarboxylate component may, lf desired, be omltted from oral preparatlons formulated to operate at such pH of 7.0 or below. Such omlsslon however could reduce the versatlllty !'and antlcalculus effectlveness of the present oral composltions over the i, I
iibroad pH range of nbout 4.5 to about lO.
In oral preparatIons such as mouthwashes, lozenges and chewing ¦
11 gum, the fluorlne-provldlng compound may be typlcally present ln an iianount sufflclent to release up to about 500 ppm, preferably about 25 to ijabout 300 ppm by welght of fluorlde ion. Generally about 0.005 to about ijl-O wt.X of such compound is present.
, In certaln hlghly preferred forms of the invention the oral compOsltlon may be substantially llquld ln character, such as a mouthwa6h or rlnse. In such a preparatlon the vehlcle 18 typlcally a water-alcohol mlxture deslrably lncludlng a humectant as descrlbed below. Generally, the welght ratlo of water to alcohol 18 ln the range " !
" ' :
1l -14-327~2 ol from about l:1 to aDout 20:1, preferably about 3:1 to lO:l and more ~preferably about 4:1 to about 6:i. The totai amount of water-alcohol ¦mlxture ln this type of preparatlon ls typlcally ln the range of from ! about 70 to about 99.9X by weight of the prepar~tlon. The alcohol 18 ltypically ethanol or isopropanol. Ethanol is preferred.
¦ The pH of such llquid and other preparatlons of the inventlon iis generally ln the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pH 18 preferably ln the range of from about 6 ¦to about 8Ø It 18 noteworthy that the composltlons of the lnvention jmay be applled orally at a pH below 5 wlthout substantlally decalclfying !1 or otherwise damaglng dentsl enamel. The pH can be controlled wlth acld (e.g. cltrlc acid or benzolc acid) or base (e.g. sodlum hydroxlde) or buffered (as wlth sodlum cltrate, benzoate, carbonate, or blcarbonate, !!dlsodlum hydrogen phosphate, sodium dlhydrogen phosphate, etc.).
jj In certaln other deslrable forms of thls lnventlon, the oral ;,composltlon may be substantially solid or pasty ln character, such as ! toothpowder, a dental tablet or a dentlfrlce, that 18 a toothpaste (dental cream) or gel dentifrlce. The vehlcle of such solid or pasty ~oral preparatlons generally contalns dentally acceptable pollshing i material. Examples of pollshlng ~aterials are water-insoluble sodlum metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated alcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, lmagensium orthophosphate, trlmagnesium phosphate, calcium carbonate, ¦alumlnum sll~cate, zlrconium silicate, silica, bentonite, and mixtures Ithereof. Other suitable polishing materlal lnclude the partlculate i! ther~osettlng reslns descrlbed ln U.S. Pat. No. 3,070,510 of Dec. l5, 1962 such aR melamlne-, phenollc, and urea-formaldehydes, and ,cross-llnked polyepoxldes and polyesters. Preferred pollshlng materlals lnclude crystalllne slllca havlng partlcle slzed of up to about 5 l !
,1 , ` 11 -15-'i, ;
. I
'" 11 3279~2 mlcron6~ a mean partlcle 6ize or up tu about 1.1 microns, and a surface area of up to about 50, 000 cm.2/gm., sillca gel or colloidal slllca, I and complex amorphous alkali metal alumlnosllicate.
When vlsually clear gel6 are employed, a poll6hlng agent of colloidal silica, 6uch as those sold under the trademark SYLOID as ¦¦Syloid 72 and Sylold 74 or under the trademark SANTOCEL as Santocel 100 alkali metal almuino-silicate complexes are particularly useful, since Ithey have refractlve lndices close to the refractlve lndlces of gelling ¦jagent-liquld (including water and/or humectant)system6 commonly used in Identifices.
Many of the so-called 'water-insoluble" polishing materials are li i anionic in character and alsv lnclude small a~ounts vf soluble material.
~Thus~ lnsoluble sodlum metaphosphate may be formed in any sultable ¦manner as illustrated by Thorpe's Dlctlonary of Applied Chemlstry, Volume 9, 4th Edltlon, pp. 510-511. The forms of lnsoluble sodlum ,metaphosphate known as Nadrell's salt and Rurrol's salt are further ¦examples of sultable materlals. These metapho6phate salt6 exhiblt only ;la mlnute solubility in water, and therefore are commonly referred to as ¦insoluble metaphosphate6 (IMP). There is present therein a minor amount ¦¦of soluble phosphate material as lmpurltles, usually a few percent such jlas up to 4% by wei8ht. The amount of soluble phosphate materlal, whlch Ills believed to lnclude a soluble sodlum trlmetaphosphate in the case vf ! insoluble metaphosphate~ may be reduced or elimlnated by washlng wlth ~¦water if deslred. The lnsoluble alkall metal metaphosphate ls typlcally employed ln powder form of a partlcle slze such that no more than 1% of ¦
!! the materlal 18 larger than 37 mlcrons.
I The pollshlng materlal ls generally pre6ent ln the solld or Ipasty composltlons ln welght concentratlons of about lOZ to about 99%.
Preferably, lt 18 present in amounts ranging from about lOZ to about 75% ¦
Il I .~
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!
! ~
~: ~: ll 13279~2 'in toothpaste, and from about 700 to about 99% in toothpowder.
! In a toothpaste, the llquid vehicle may comprise water and ¦humectant typically ln an amount ranglng from about IOX to about 80Z by weight of the preparation. Glycerine, propylene glycol, sorbitol, I!polypropylene glycol ant/or polyethylene glycol (e.g. 400-600) exemplify ;Isuitable humectants/carrier6. A180 advantageous are liquit ~ixtures of Iwater, glycerine and sorbitol. In clear gels where the refractive index jis an important con6ideration, about 3-30 wt. % of water, O to about 70 ¦wt.X of glycerine and about 20-80 wt. % of sorbltol are preferably employed.
~! Toothpastes, creams and gels typically contain a natural or l6Ynthetic thickener or gelling agent in proportions of about 0.1 to ¦!about 10, preferably about 0.5 to about 5wt.%. A suitable thickener is l6ynthetic hectorite, a synthetic colloltal magne61um alk li metal ~sllicate complex clay available for example as Laponite (e.g. CP, SP
~i2002,D) marketed by Laporte Industries Limitet. Laponite D analysis show6, approximately by weight, 58.00X SiO2, 25.40X MgO, 3.05Z Na20, .98~ Li20, and some water and trace metals. Its true specific gravity is 2.53 and it has an apparent bulk density (g./ml. at 8% moisture) of ~-o-Other suitable thickeners include Irish moss, gum tragacanth, 'Istarch, polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl ¦ llmethyl cellulo6e, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g. available as Natrosol), sodium carboxymethyl cellulose, and icolloidal silica such as finely ground Syloid (e.g. 244).
It will be understood that, as is conventional, the oral . I
preparations are to be sold or otherwise distributed ln suitable labelled packages. Thus a ~ar of mouthrinse will have a label de6cribing it, in substance, as a mouthrinse or mouthwash and having 1~ r~e-~ I
. i .~, 11 1.
~ !1 13279~2 ,j dlrections for ltæ u~e; and a eoothpaste, cream or gel will u~ually be ¦¦ in ~ collapsible tube, typically aluminum, lined lead or plastic, or other ~queeze, pump or pressurized dlspenser for meterlng out the contents, havlng a label descrlblng it, ln substance, as a toothpaste, j gel or dental cream.
Organic surface-active agents are used in the compositions of the present invention to achieve increased prophylactic action, assist ln achieving thorough and complete dispersion of the anticalculu~ agent ¦ throughout the oral cavity, and render the lnstant compo6itlon6 more cosmetically acceptable. The organic 6urface-active material is preferably anionlc, nonionic or ampholytic In nature, and it i6 !! preferred to employ as the surface-active agent a detersive material !¦ which lmparts to the composition detersive and foaming properties.
Sultable e~camples of anionic ~urfactants are water-soluble salts of ¦higher fatty acld monoglyceride monosulfates, such as the sodium salt of the monosulfatet monoglyceride of hydrogenated coconut oil fatty acids, 1 ~ ¦
'! higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl ~1 sulfonates wch as 60dium dodecyl benzene sulfonate, higher alkyl ulfoacetate6, higher fatty acid esters of 1,2-dihydroxy propane ¦ 6ulfonate, and the substantlally 6aturated higher aliphatic acyl amide6 j¦ of lower aliphatlc amino carboxylic acid compounds, such as those having Il 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the . i i! like. Example~ of the la6t mentioned amide6 are N-lauroyl sarco6ine, .i ' !l and the 60dium, pota66ium, and ethanolamine salt6 of N-lauroyl, . . ~
'i N-myristoyl, or N-palmitoyl sarcosine which should be substsntially free j from 60ap or similar higher fatty acid material. The use of these , ¦
sarcosinate compounds in the oral compositions of the present lnvention partlcularly advantageous since these materlals exhibit n prolonged !! and marked effect ln the inhibition of acid formatlon ln the oral cavlty ~i , 1", `- 1 3 2 7 9 ~ 2 -~ due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydro-phobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydr c alcohols (e.g. sobitan mono-C sterate) and polypropyleneoxide (e.g. Pluronic materials). It is preferred to use from about 0.05 to 5% by weight and preferably about 0.5 to 5% of the foregoing surface active materials in the instant compositions.
Various other materials may be incorporated in the oral prepar-ations of this invention such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated material such as urea, diammonium phosphate, and mixtures thereof.- These adjuvants, where present, are incorporated in the preparations in amounts which do not substantially adversely affect the properties and characteristics desired. Significant amounts of ~inc, magnesium and other metal salts and materials, generally soluble, which would complex with active components of the instant invention are to be avoided.
Any suitable flavoring or sweetening material may also be employed.
Examples of suitable flavoring constituents are flavoring oils, e.g. oil of spearmint, peperment, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon~ and orange~ and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitil, xylitol, sodium cyclamate, perillartine, AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.1% to 5% more of the preparation.
In the preferred practice of this invention an oral composition ~ I ra~
:
l! I
~ ;l 13279~2 1l!
~according to this lnvention such as a mouthwash or den~ifrlce contalning ithe composition of the present inventlon i6 preferably applied regularly to dentsl enamel, such as every day or every second or third day or preferably from 1 to 3 tlmes daily, at a pH of about 4.5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up to llfetime.
The compositions of this lnvention can be incorporated in lozenges, or in chewing gum or other products, e.g. by stirring into a warm gum base or coating the outer surface of a gum bage, illustrative ' of which may be mentioned ~elutone, rubber latex, vinylite resins, etc., I
, desirably with conventional plasticizers or softeners, sugar or other ~ ~j ;i Isweeteners or carbohydrates such as glucose, sorbitol and the like.
j The following examples are further illu~trative of the nature ' ! of the present lnvention, but it is under~tood that the invention 18 not ,limited thereto. All amounts and proportlons referred to herein and in the appended claims are by welght. ¦
., I ,,~.
.~
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!l ~ 20-`s 1 !
~, . i 1~27942 E~ample I
¦¦ Slurries and golutions tescrlbed below are prepared to determine ~effectiveness ln terms of minlmum lnhlb~tory concentratlon (MIC) of ~¦various antlbacterlal agents agalnst a variety of oral bacterlal organisms lmpllcated in format$on of plaque and leadlng to glngivitl6 on dental surfaces. Soft plaque contalns about 1.7 x 101l organism/gm.
(net weight). The antibacterlal agents are admlxed wlth anlonlc materlals, partlcularly anlonic surface actlve agent often commonly employed in oral composltlons and polyphosphate antlcalculus agent.
Minimum inhlbitory concentratlon (MIC) of antlbacterial agent ¦
jls used to evaluate the efficacy of the agent ln vltro. MIC is deflned ;~as the mlnlmum concentratlon ln mlcrograms/ml of antlbacterlal agent at ¦whlch the growth of bacterla 18 completely lnhlblted by the agent. The ;smaller the MIC value the greater is the efficacy of the antlbacterlal ! agent to lnhlblt the growth of the bacterla. The ln vltro MIC data 18 'Ir~lated to the efflcacy of the dentlfrlce ln vlvo slnce retentlon and release of antlbacterlal agent lnto the oral cavlty after toothbrushlng i8 ln the range of mcg/ml-¦¦ In the Tables, followlng dlsclosure and following E~amples, the agent Trlclosan, 2,4,4'-trlchloro-2'-hytroxydlphenyl ether 18 lndlcated I!as "TCHE"; the quaternary ammonlum antlbacterlal agents benzthonlum !
ilchlorlde 18 lndlcated a6 BTC ; The blguanlde chlorhexldlne dlgluconate ¦
ls lndlcated as "CH , sodlum lauryl sulfate 18 lndlcated as SLSn; the copclymer of malelc anhydrlde and methyl vlnyl ether avallable from GAF
i!corporatlon as "Gantrez S-97" is identifled as "Gantrezn; tetrasodium i! pyrophosphate 18 identifled as "pyrophosphate ; and sodlum fluorlde ls l! ldentlfled as "~aF".
~1 !
~ -21- !
Il . i, Il ji il ,1 13279~2 li TABLE 1 Il .
I Minlmum Inhlbltlon Concentratlon Test (MIC) ISolutlon ln mcg/ml ,j Bacterlode~ Bacterlodes Actlnobaclllus Streptococcu6 glnglvall6 lntermedlus actlnomycetem- mutanR
comitans jl. 0.5% TCHE and 2.5 2.5 5.0 25.0 , l~ SLS ln ! water j~2. 0.5% TCHE, 2.5 2.5 5.0 25.0 i lX SLS, ! I% Gaotrez, l 2X Pyrophosphate I and 0.2% NaF ln ! water l3- 1% SLS in NE NE NE NE
!i water 4. lX SLS, NE NE NE NE
lX Gantrez and 2X Pyrophosphate ll in water ¦¦note: NE ~ not effectlve .I , , j The regults lndlc-te that TCHE ln the presence of anlonlc surfactant lnhlbltet four dental plsque organlsms, Bacteriodes glngivalis, Bacterolte~ lntermedlus, Actlnobaclllus - -actlnomyretemcomlt-ns and Strep. DDe-D~ at 2.5 mcg/ml and 2.5 ~cg/ml, ~1 15.o mcg/ml and 25.0 mcg/ml re~pectively(I). Slmilar antlbacterlal effect i8 seen ln the presence of Gantrez/pyrophosphate/fluoride(2).
i SLS per se and a combination of SLS/Gantrez/pyrophosphate/fluoride wa~
;~ ineffectlve(3 ant 4).
It i8 noteworthy that in human clinical tests with cationic antibacterial agents, 0.075% BTC dissolved in water is effective ln ¦reducing plaque formation while 0.075~ BTC and 1~ pyrosphosphate ~!dissolved in water is not. Simil-rly, O.OlX CH dissolved in water is ¦effective in retuclng plaque formation while 0.01% CH and 1% sotium N-lauroyl ~arcosinate dissolved in water 18 not.
!!
~ I -22-, I
11 13279~2 !l I
'' Example 2 ,, The adsorption to and release from tooth mineral6 for sntiplaque/ ~ntltartar efflcacy of agents is assesset by atsorptlon of an~ibacterial agent to saliva coated tooth mineral hydroxyapatite ln the presence ant the absence of pyrophosphate (soluble tetrasodlum pyroph~sphate)tGantrez/NaF.
200 mg. of hydroxyapatlte (HA) is treated with human ~aliva for 2 hours. The excess saliva 18 washed off with a buffer and saIiva coated HA
is used for adsorption studies. Variou~ concentratlons of TCHE in SLS
~or in SLS/pyrophosphate/Gantrez/NaF are mixed with the coated HA and lnc~bated at 37 for 3 hours under continuous agitation. At the end of iincubation period, the mixture6 are centrifuged, HA separatet and the ij amounts of TCHE adsorbed determined by estimating TCHE in the 'Isupernatant at 283nM in a Gilford spectrophotometer. The amounts l~¦adsorbed are calculated by the difference between the amount added and j¦the amount left ln the supernatant after the lncubation with coated HA.
The table below summarizes the data.
1l 1 .i . ' '. ,i , I
,, 1 ;~ jj i l! I
Il -23-i 3;27~2 I, TABLE 2 Il I , ~'Co~eonents and Concentratlons % of TCHE Adsorbed to Coated HA
.5Z TCHE ln lX SLS 80X
O.OIX TCHE in 1% SLS 85%
j0.015Z TCHE in 1~ SLS 85%
0.02X TCHE ln lZ SLS 88%
0.005% TCHE ln lX SLS; 0.5% 80%
Gantrez, 2X pyrophosphate/ ! ::
0.24X NaF
'IO~OlX TCHE ~ 85X
:, I :'"' ;,0.015X TCHE " 86X I -~
0.02Z TCHE " 87%
ll The tata lndlcates that the addltlon of pyrophosphate/
i I I
Gantrez/NaF does not lmpalr adsorption of TCHE to sallva coated tooth ~minerals.
,, i ! i -1! I
!¦ l i j 1 , 1.
,1 , 1~ -24-: :~
: :
Example 3 ¦iDentlfrice Composltlons A B C
Parts Parts Parts Glycerine 15.00 10.20 15.00 ¦Polyethylene Glycol 600 5.00 3.00 5.00 ,lv~a Carrageenan 0.60 - 0.60 ISodium Carboxymethyl Cellulose - 1-00 Sodlum Saccharin 0.40 - 0.40 ,,Sodlum Cyclamate - 3.00 - I ~:
j;Sodium Fluoride 0.243 0.243 0.243 .. I
Deionlzed water 15.08 29.907 23.657 Titanlum Dio~ite - - 0.50 lsodlum Benzoate - 0.50 ~iFD&C Blue No. 1(1% Solutlon) 0.400 : j,Sorbltol (70~) 19.807 22.50 22.50 ~ Gantrez S-97 8.330t*) 1.00(**) 1.00(**) 1 :
; IjTetrasotlum Pyrophosphate1.50 1.50 1.50 : ¦!Tetrapotasslum Pyrophosphate 4.50 4.50 4.50 Preclphatet Amorph. Hydrated Silica 16.00 19.50 ~ IIPreciphated Amorp. Silica - - 16.00 7 ¦i containing combined alu~ina i : ,jSllica Thickener 7.00 - 5.50 jjFlavor 1.10 0.95 1.10 otlum Lauryl Sulfate 1.20 1.20 1.20 3~ iiTCHE 0 50 0 50 0.50 * liquld '!** powter '~ il I
~ ! i ,';
~ -25-1~27~2 Example 4 The dentifrlce descrlbed ln Example 3A 16 compared with the ~ame compositlon except without any TCHE and wlth added 0.50 parts of vater. Aqueous extracts of each dentlfrlce are prepared as follows: 50 ml of dlstllled water i8 added to 1.0 gm of each déntlfrlce, mlxed well for a couple of hours with stlrrlng bar and centrifuged, after which the ~upernatant i6 collected as aqueous extract. Antlbacterlal actlvlty of ;~
the dentifrlce extracts are evaluated on Bacterlodes gingivalls. -;~
Results are summarized below.
TA8~E 3 Inhlbltion of Growth of Bacterlodes Glnglvalls Tr~at~ent ~ _ Extract from dentifrice contalnlng 100.0 TCHE (1:500) Extract from dentlfrlce wlthout 0.0 TCHE (1:509) TCHE (5.0 mcg/ml) by itself 100.0 '-Ihese results lndlcate that TCHE antlbacterlal antlplaque agent is compatible ln a dentifrice composltion contalnlng anlonic surfactant plus pyrophosphate antlcalculus lngredients wlth enzyme inhibltors Cantrez and NaF. Simllar comparable effects prevall when each of hexyl resorcinol, 2,2'-methylene bls~4-chloro-6-bromophenol)/
replace TCHE.
, .
.~ .
.
13279'12 j ~xample 5 M uthrinse Part_ Tetrasodium Pyropho6phate 2.00 ~!Gantrez S-97 0.25 j¦Glycerine 10.00 ¦¦Sodlum Fluoride 0.05 Pluronic* F108 2.00 - (Polyoxyethylene/Polyoxypropylene Block Copolymer) ITCHE o.lo Flavor 0.40 ~!water Q.S. to 100.00 Example 6 Lozenge 75-80% Sugar 20% Corn Syrup ,10.1-1.0 Flavor 2% Tetrasodium Pyrophosphate ji0.25X Gantrez S-97 '0.01 to 0.05X NaF
¦¦0.01 to O.lZ TCHE
1 to 5X Magne6ium Stearate Lubricant ',0.01 to 0.2Z Water ! *Trade Mark !
1, l!
jj I!
i.l ! Examnle 7 r ;l I
Chewing Gum Parts ! Gum base 25.00 . Sorbltol (70X) 17.00 TCHE 0.50 to 0.10 Tetrasodium Pyrophosophate 2.00 Gantrez S.97 0.25 ,NaF 0 05 ~Glycerine o.5o ICrystalline Sorbitol 53.00 " Flavor and Water Q.S. to 100.00 This invention has been described wlth respect to certain ¦preferred embodiments and it will be understood that modifications and .jvariations thereof obvious to those skilled ln the art are to be lincluded within the purview of this application and the scope of the j! appended claims.
!l Il I
11 i 1l!
., I
., ,i . I
: 11 1 :` l 1.
11 -28- ~
Claims (18)
1. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphos-phate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000.
2. The oral composition according to Claim 1 wherein said polyphosphate salt comprises sodium tripolyphosphate.
3. An oral composition according to Claim 1 wherein the substantially water-insoluble noncationic antibacterial compound is a phenolic compound.
4. An oral composition according to Claim 3 wherein said antibacterial phenolic compound comprises hexyl resorcinol.
5. An oral composition according to claim 4 wherein said polyphosphate salt comprises sodium tripolyphosphate.
6. An oral composition according to Claim 5 further containing as essential inhibitor of salivary enzymatic hydrolysis of the sodium tripolyphosphate in an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
7. The oral composition according to Claim 6 wherein said water-soluble polycarboxylate salt is an alkali metal or ammonium salt of a copolymer of vinyl methyl ether and maleic acid or anhydride having a molecular weight of about 30,000 to about 500,000.
8. The oral composition according to Claim 7 in the form of a toothpaste containing a dentally acceptable water-insoluble polishing agent.
9. The oral toothpaste composition according to Claim 8 containing a silica polishing agent.
10. An oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphos-phate salt as essential anticalculus agent, and effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent and:
A) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate; or B) mixtures of A) and an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
A) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate; or B) mixtures of A) and an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
11. An oral composition according to Claim 10 containing B wherein said fluoride ion-providing source which comprises sodium fluoride, sodium monofluorophosphate, or a mixture thereof.
12. An oral composition according to Claim 10 containing B wherein said fluoride ion-providing source comprises sodium fluoride, sodium monofluorophosphate or a mixture thereof and said polycarboxylate comprises a salt of a copolymer of maleic acid or anhydride with methylvinylether.
13. An oral composition according to Claim 12 wherein said antibacterial compound comprises a halogenated diphenyl ether.
14. An oral composition according to Claim 13 wherein said antibacterial compound comprises Triclosan.
15. An oral composition according to any one of Claims 10 to 14 in the form of a toothpaste, cream or gel containing a dentally acceptable polishing agent.
16. An oral composition according to any one of Claims 10 to 14 in the form of a mouthwash containing a water humectant vehicle.
17. An oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent and:
A) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate; or B) mixtures of A) and an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
A) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate; or B) mixtures of A) and an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
18. Use of an oral composition according to any one of Claims 1 to 14 and 17 to combat calculus and plaque in a mammal.
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA000616608A CA1328623C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
CA000616610A CA1328081C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
CA000616760A CA1339301C (en) | 1987-01-30 | 1993-11-04 | Antibacterial antiplaque, anticalculus oral composition |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US890187A | 1987-01-30 | 1987-01-30 | |
US008,901 | 1987-01-30 |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000616610A Division CA1328081C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
CA000616608A Division CA1328623C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
CA000616760A Division CA1339301C (en) | 1987-01-30 | 1993-11-04 | Antibacterial antiplaque, anticalculus oral composition |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1327942C true CA1327942C (en) | 1994-03-22 |
Family
ID=21734350
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000557661A Expired - Lifetime CA1327942C (en) | 1987-01-30 | 1988-01-29 | Antibacterial antiplaque, anticalculus oral composition |
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US (1) | US5037635A (en) |
JP (1) | JP2528492B2 (en) |
AR (1) | AR243371A1 (en) |
AT (1) | AT395109B (en) |
AU (5) | AU7423891A (en) |
BE (1) | BE1001110A5 (en) |
BR (1) | BR8800360A (en) |
CA (1) | CA1327942C (en) |
DE (1) | DE3802168B4 (en) |
DK (1) | DK174455B1 (en) |
ES (1) | ES2010740A6 (en) |
FI (1) | FI97329C (en) |
FR (6) | FR2610195B1 (en) |
GB (4) | GB2200551B (en) |
GR (1) | GR1000112B (en) |
HK (1) | HK89194A (en) |
IN (1) | IN168400B (en) |
IT (1) | IT1219830B (en) |
MX (1) | MX163856B (en) |
MY (1) | MY103169A (en) |
NL (1) | NL195088C (en) |
NO (1) | NO174572C (en) |
NZ (1) | NZ223125A (en) |
PE (1) | PE12991A1 (en) |
PH (1) | PH24874A (en) |
PT (1) | PT86661B (en) |
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US4022880A (en) * | 1973-09-26 | 1977-05-10 | Lever Brothers Company | Anticalculus composition |
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US4701319A (en) * | 1984-09-14 | 1987-10-20 | The Procter & Gamble Company | Toothpaste compositions |
US4661341A (en) * | 1984-10-30 | 1987-04-28 | The Procter & Gamble Company | Oral compositions |
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DE3607480A1 (en) * | 1986-03-07 | 1987-09-10 | Blendax Werke Schneider Co | TOOTHPASTE |
GB8615534D0 (en) * | 1986-06-25 | 1986-07-30 | Beecham Group Plc | Composition |
GB8629640D0 (en) * | 1986-12-11 | 1987-01-21 | Beecham Group Plc | Composition & method |
US4894220A (en) * | 1987-01-30 | 1990-01-16 | Colgate-Palmolive Company | Antibacterial antiplaque oral composition |
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-
1987
- 1987-12-30 IN IN1148/DEL/87A patent/IN168400B/en unknown
-
1988
- 1988-01-06 MY MYPI88000007A patent/MY103169A/en unknown
- 1988-01-07 NZ NZ223125A patent/NZ223125A/en unknown
- 1988-01-08 ZA ZA88130A patent/ZA88130B/en unknown
- 1988-01-26 DK DK198800371A patent/DK174455B1/en not_active IP Right Cessation
- 1988-01-26 DE DE3802168A patent/DE3802168B4/en not_active Expired - Lifetime
- 1988-01-27 GB GB8801773A patent/GB2200551B/en not_active Expired - Lifetime
- 1988-01-28 NL NL8800206A patent/NL195088C/en not_active IP Right Cessation
- 1988-01-29 FI FI880425A patent/FI97329C/en active IP Right Grant
- 1988-01-29 BE BE8800107A patent/BE1001110A5/en not_active IP Right Cessation
- 1988-01-29 AT AT0018688A patent/AT395109B/en not_active IP Right Cessation
- 1988-01-29 PT PT86661A patent/PT86661B/en not_active IP Right Cessation
- 1988-01-29 IT IT47582/88A patent/IT1219830B/en active
- 1988-01-29 FR FR888801070A patent/FR2610195B1/en not_active Expired - Lifetime
- 1988-01-29 MX MX10260A patent/MX163856B/en unknown
- 1988-01-29 NO NO880410A patent/NO174572C/en unknown
- 1988-01-29 BR BR8800360A patent/BR8800360A/en not_active Application Discontinuation
- 1988-01-29 PH PH36431A patent/PH24874A/en unknown
- 1988-01-29 CA CA000557661A patent/CA1327942C/en not_active Expired - Lifetime
- 1988-01-29 ES ES8800251A patent/ES2010740A6/en not_active Expired
- 1988-01-30 JP JP63021145A patent/JP2528492B2/en not_active Expired - Fee Related
- 1988-02-01 SE SE8800299A patent/SE503827C2/en not_active IP Right Cessation
- 1988-02-01 GR GR880100046A patent/GR1000112B/en not_active IP Right Cessation
- 1988-02-01 AR AR88309988A patent/AR243371A1/en active
-
1989
- 1989-11-13 US US07/436,155 patent/US5037635A/en not_active Expired - Lifetime
- 1989-12-20 PE PE1989163121A patent/PE12991A1/en unknown
-
1990
- 1990-02-01 FR FR909001188A patent/FR2640134B1/en not_active Expired - Lifetime
- 1990-04-04 GB GB9007575A patent/GB2230189B/en not_active Expired - Lifetime
- 1990-04-04 GB GB9007574A patent/GB2230188B/en not_active Expired - Lifetime
- 1990-04-04 GB GB9007573A patent/GB2230187B/en not_active Expired - Lifetime
- 1990-05-03 FR FR909005591A patent/FR2647011B1/en not_active Expired - Lifetime
- 1990-05-03 FR FR909005588A patent/FR2647010B1/en not_active Expired - Lifetime
- 1990-05-03 FR FR909005587A patent/FR2647013B1/en not_active Expired - Lifetime
-
1991
- 1991-04-09 AU AU74238/91A patent/AU7423891A/en not_active Abandoned
- 1991-04-09 AU AU74239/91A patent/AU629743B2/en not_active Expired
- 1991-04-09 AU AU74236/91A patent/AU630028B2/en not_active Expired
- 1991-04-09 AU AU74235/91A patent/AU629742B2/en not_active Ceased
- 1991-04-09 AU AU74237/91A patent/AU631056B2/en not_active Expired
- 1991-11-29 FR FR9114843A patent/FR2669532B1/en not_active Expired - Fee Related
-
1994
- 1994-08-25 HK HK89194A patent/HK89194A/en not_active IP Right Cessation
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